The physiological response to steroid hormones is mediated by specific interactions of steroids with nuclear receptors, which are ligand-activated transcription factors that regulate the expression of target genes by binding to specific DNA response elements. These receptors comprise (in an aminoterminal-to-carboxyterminal direction) a hypervariable aminoterminal domain that contributes to the transactivation function; a highly conserved DNA-binding domain responsible for receptor dimerization and specific DNA binding; and a carboxyterminal domain involved in ligand-binding, nuclear localization, and ligand-dependent transactivation.
Recently, cDNA was cloned from rat prostate and was shown to have significant homology to a previously isolated rat estrogen receptor cDNA. Kuiper et al., Proc.Natl.Acad.Sci.USA 93:5925, 1996. This receptor was designated ERβ to distinguish it from a previously cloned receptor, ERα. Rat ERβ was shown to be expressed in the prostate, testes, ovary, and thymus, in contrast to ERα, which is most highly expressed in the uterus, breast, liver, and pituitary.
A human ERβ homologue having the aminoterminal sequence Gly-Tyr-Ser has been reported. Mosselman et al., FEBS Letts. 392:49, 1996. This reported sequence lacks an initiator methionine, however; therefore, the complete aminoterminal sequence could not be determined. Thus, the full-length human gene remained unknown and an accurate picture of the molecular determinants of the transactivation function of authentic hERβ could not be obtained.